The 'α-synucleinopathy syndicate': multiple system atrophy and Parkinson's disease

Abstract

Multiple System Atrophy (MSA) and Parkinson's diseases (PD) are elite members of the α-synucleinopathy organization. Aberrant accumulations of the protein α-synuclein characterize them. A plethora of evidence indicates the involvement of these rogue inclusions in a cascade of events that disturb cellular homeostasis resulting in neuronal dysfunction. These two neurodegenerative diseases share many features both clinically and pathologically. Cytotoxic processes commonly induced by reactive free radical species have been associated with oxidative stress and neuroinflammation, frequently reported in both diseases. However, it appears they have characteristic and distinct α-synuclein inclusions. It is glial cytoplasmic inclusions in the case of MSA while Lewy bodies manifest in PD. This is probably related to the etiology of the illness. At present, precise mechanism(s) underlying the characteristic configuration of neurodegeneration are unclear. Furthermore, the "prion-like" transmission from cell to cell prompts the suggestion that perhaps these α-synucleinopathies are prion-like diseases. The possibility of some underlying genetic foul play remains controversial. But as major culprits of pathological processes or even single triggers of PD and MSA are the same-like oxidative stress, iron-induced pathology, mitochondriopathy, loss of respiratory activity, loss of proteasomal function, microglial activation, neuroinflammation-it is not farfetched to assume that in sporadic PD and also in MSA a variety of combinations of susceptibility genes contribute to the regional specificity of pathological onset. These players of pathology, as mentioned above, in a synergistic combination, are responsible for driving the progression of PD, MSA and other neurodegenerative disorders. Elucidating the triggers and progression factors is vital for advocating disease modification or halting its progression in both, MSA and PD.

Keywords: Glial cytoplasmic inclusions; Lewy bodies; Multiple system atrophy; Neurodegeneration; Parkinson’s disease; Pathomechanisms; α-synuclein.